Preterm infants are at high risk for developmental impairments at school age. However, the impact of these impairments on important life skills, such as handwriting, is unknown. Forty-eight first-grade children (27 males, 21 females; mean age 6y 7mo, SD 3.9mo; range 6y 1mo to 7y 3mo) born preterm (birthweight <1250g; gestational age <34wks), without major physical or cognitive disabilities, were matched to 69 healthy, term control children (32 males, 37 females; mean age 6y 10mo, SD 3.6mo; range 6y 3mo to 7y 4mo) by sex and school class. All children were assessed using the Evaluation Tool of Children's Handwriting-Manuscript and several sensorimotor measures. Preterm children demonstrated significantly lower legibility and slower speed scores (p<0.01) compared with control children for most of the handwriting tasks. Factors associated with legibility were visual perception and eye–hand coordination (r[les ]0.50; p<0.05) and sex (r[les ]0.12; p=0.01). In-hand manipulation and finger identification (r[les ]0.43; p<0.01) were significantly correlated with slow handwriting speeds. Behaviour difficulties associated with hyperactivity and poor attention (Connors Abbreviated Symptoms Questionnaire) had a confounding influence on both legibility and speed. These findings may help guide early identification efforts and medical/therapeutic interventions for preterm children.

In this study of 118 children (median age 5.1 years; range 6 months to 17 years) with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocysteine concentration in homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who were negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly more likely to have a recurrent event than those who were negative or heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozygosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA.

First-onset tics during stimulant treatment of attention-deficit–hyperactivity disorder (ADHD) are clinically relevant and remain a matter of scientific debate. Because there are limited clinical trials analyzing the risk of first-onset tics in stimulant-treated ADHD, a comprehensive evaluation is required for evidence-based clinical recommendations. An analysis of studies with high methodological quality (i.e. double-blind placebo-controlled) on first-onset tics during stimulant treatment of ADHD revealed that there seems to be no elevated risk of first-onset tics in children undergoing this treatment. Although a close temporal relationship might be seen in a few patients, the role of treatment duration, dose of stimulant, genetic vulnerability, and developmental aspects need to be further explored to clarify possible pathophysiological mechanisms of tic emergence under stimulant treatment. The results of high quality studies, in addition to specialized studies with methodological limitations, suggest that stimulants are the criterion standard for the safe and successful treatment of ADHD.

We describe the clinical presentation, course, and treatment response of a 14-year-old boy with catatonic stupor. This patient, with a preexisting diagnosis of autism, displayed mutism, akinesia, and an extreme level of rigidity, waxy flexibility, posturing, including the psychological pillow, facial grimacing, and other involuntary movements of his upper extremities. In addition he had symptoms suggestive of a depressive disorder as well as some non-specific psychotic symptoms. Intravenous injection of sodium amytal failed to resolve any motor symptoms, although he showed a good response to the zolpidem test. A course of electroconvulsive therapy (ECT) caused dramatic and sustained relief of catatonic stupor without a change in the symptoms of autism. The presentation of catatonia in autism and the use of ECT in children are discussed, and the available literature reviewed. This is the first description of the use of ECT in the treatment of catatonia coinciding with autism and we confirm its efficacy.

The objective of this study was to explore the behaviour, including sleep patterns, of children with neurofibromatosis type 1 (NF1). For this purpose we designed a cross-sectional descriptive survey conducted by postal enquiry with telephone follow-up. Simonds and Parraga's sleep questionnaire and the Strength and Difficulties Questionnaire were used to screen sleep patterns and behaviours respectively. Information was obtained for 64 children (39 male, mean age 10y 7mo, SD 4y 1mo, range 3 to 18y; 57% response rate). There were increased numbers of children with NF1 achieving scores in the borderline and abnormal range for ratings of peer problems (p<0.001), hyperactivity (p<0.001), emotional symptoms (p<0.001), and conduct disorder (p<0.05). Total difficulties score was also high (p<0.001) in the NF1 group. Only one group of sleep problems, parasomnias (in particular sleepwalking and sleep terrors), had a higher occurrence (p[les ]0.05) in the NF1 group than in the general population. Within the NF1 group, conduct problems (p[les ]0.05), hyperactivity (p[les ]0.01), emotional problems (p[les ]0.01), and the total difficulties score (p[les ]0.01) were all significantly higher in children with frequent sleep disturbance. We conclude that NF1 is associated with sleep and behavioural problems in a high proportion of children. Psychiatric conditions, e.g. attention-deficit–hyperactivity disorder, may be under-diagnosed on a large scale in children with NF1, and the use of simple screening tools in clinical settings may prove beneficial.

A study of 37 individuals with phenylketonuria (PKU; 17 females and 20 males, mean age 9y 9mo (standard deviation [SD] 5y 3mo), range 2y 8mo to 19y 4mo; and 35 individuals with hyperphenylalaninaemia (HPA; 20 females, 15 males, mean age 7y 10mo [SD 3y 2mo], range 2y 8mo to 17y 3mo) compared with 29 healthy controls (14 females and 15 males, mean age 9y 8mo [SD 4y 9mo], range 2y 6mo to 18y 10mo) was performed. The aim was to assess cognitive function in persons with HPA and to investigate the relation between cognitive function in PKU and the metabolic control of patients. A wide variety of neuropsychological tests was employed. Those with PKU showed lower values in intelligence and in visuo-spatial, fine motor, executive, and attention functions when compared with a control population. Plasma phenylalanine values from the first 6 years of life were negatively associated with intelligence and other cognitive functions. Executive function scores were significantly lower when comparing HPA patients with the control group. It was concluded that individuals with PKU under dietary treatment may present slightly decreased cognitive function scores when compared with control individuals, while those with HPA have scores mostly similar to those of controls, except for executive function tests. Good metabolic control of PKU seems necessary to prevent cognitive function impairments, especially during the first 6 years of life.

In 1937, Orton described children with motor coordination difficulties as ‘clumsy’, a term still used today. Other terms used to describe these difficulties include developmental dyspraxia, awkwardness, motor learning problems, and most recently, developmental coordination disorder (DCD). DCD is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a ‘marked impairment in the development of motor coordination [that]... interferes with academic achievement or activities of daily living’. The impaired coordination is present in the absence of a known medical condition such as cerebral palsy or muscular dystrophy. The heterogeneity of the motor and cognitive abilities of children included in this classification, and the numerous terms employed to describe them, have hindered systematic accumulation of knowledge about DCD.

The present study addressed the question whether the deviant postural adjustments in children with spastic diplegia can be attributed to their crouched sitting position or primarily to their neural deficit. Postural adjustments during sitting in an erect and in a crouched position on a movable platform were assessed in 10 children, aged 3 to 7 years 6 months, with mild-to-severe forms of spastic diplegia and 10 age- and sex-matched control children. Multiple surface EMGs of neck, trunk, and leg muscles and kinematics of head, body sway, and pelvis were recorded during forward and backward translations. The children with normal motor development showed a distinct adaptation of postural adjustments to sitting position. The children with cerebral palsy (CP) had a deficient adaptational capacity which was more pronounced in the erect than in the crouched position. Thus, the crouched sitting position did not induce postural deficiency but seemed to offer a solution to the sensory–motor problem of the instability experienced. Children with severe diplegia exhibited a lack of direction specificity in the leg muscles during backward body sway, which points to a basic deficit in postural control. In addition, these children showed marked dysfunctions in the precise tuning of the postural adjustments to task-specific conditions. In the children with mild-to-moderate forms of CP the basic level of control was intact.

The heightened risk of epilepsy in cerebral palsy (CP) was recognized by Freud more than 100 years ago. His descriptions of the characteristics of the seizures indicate his appreciation of their essentially symptomatic nature. Much more recently, the importance of epilepsy as an adverse factor for cognitive function in children with hemiplegic CP has been highlighted. The possibility that subclinical seizure discharges may add to cognitive problems requires particular attention in any child whose abilities may be already impaired secondary to structural brain abnormalities. Nevertheless, it is important to recognize that the motor difficulties, and any intellectual disabilities, as well as complicating seizures, are likely to stem from the same underlying pathology.

Group A Streptococcus can induce autoimmune disease in humans with particular involvement of the heart, joints, and brain. The spectrum of post-streptococcal disease of the central nervous system (CNS) has been widened recently and includes movement disorders (chorea, tics, dystonia, and Parkinsonism), psychiatric disorders (particularly emotional disorders), and associated sleep disorders. Neuroimaging and pathological studies indicate that the most vulnerable brain region is the basal ganglia. The immunopathogenesis of the disease is incompletely defined, and although there is some support for autoantibody-mediated disease, several conflicting studies cast doubt on the autoantibody hypothesis. It has been speculated that post-streptococcal autoimmunity has a role in common neuropsychiatric disease but the evidence is conflicting and routine screening of patients with Tourette syndrome and obsessive–compulsive disorder for post-streptococcal autoimmune abnormalities is not be recommended at present. However, post-streptococcal disorders of the CNS remain a useful model of neuropsychiatric disease, which may improve our understanding of abnormal movements and behaviours in children.

The results of a therapeutic trial of the use of melatonin in patients with tuberous sclerosis complex who also have severe sleep problems are reported. We used a randomized double-blind placebo-controlled crossover design. Seven patients with confirmed diagnoses of tuberous sclerosis and significant sleep disorder were recruited. We employed three outcome measures: total sleep time, time to sleep onset, and number of awakenings. Patients treated with melatonin had a small but clinically significant improvement in total sleep time (mean improvement 0.55 hours, P<0.05). They also tended to have an improvement in sleep-onset time but this did not reach statistical significance. Melatonin, in this trial, had no discernible effect on sleep fragmentation. We conclude that melatonin does have a beneficial effect in prolonging the total sleep time of patients with tuberous sclerosis and sleep disorder and that further trials are necessary to investigate the issues of optimal dosage, tolerance, and possible interactions with other medications.

Damage to the occipital cortex in children can result in many complex disorders of cognitive visual function. A series of clinical questions, developed from the specific problems of a cohort of children with cortical visual impairment, was asked of the parents of 200 children with no history of cerebral pathology, aged 5 to 12 years. One hundred and ninety-two parents gave reliable consistent responses. The results show a progressive improvement in performance with age, culminating in few 11- and 12-year olds having frequent problems, apart from 8% having frequent difficulty with orientation in new surroundings and 2% having problems with simultaneous perception tasks. The parents of 52 children (aged 5 to 17 years) with shunted hydrocephalus were then asked the same set of questions. Evidence of cognitive visual problems was identified in 27 of these children of whom 16 manifested multiple difficulties. The disabilities identified by our study comprised problems with: shape recognition, simultaneous perception, perception of movement, colour perception, orientation, object recognition, and face recognition. The range, nature, and combinations of these disorders are presented in this paper.

The aim of the study was to determine whether pediatric patients with cerebral palsy (CP; 24.3% hemiplegic, 30.4% diplegic, 38.5% quadriplegic) can self-report their health-related quality of life (HRQOL) with the Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales. The PedsQL was administered to 148 families (84 males, 64 females; mean 10y, SD 3y 9mo, range 5 to 18y) recruited from a children's hospital clinic and state medical therapy clinics. Sixty-nine children (47%) were able to self-report. Children with CP self-reported a significantly lower HRQOL (mean 65.9) than healthy children (mean 83.8). Children with CP self-reported a similar HRQOL to pediatric cancer patients receiving treatment (mean 68.9). Children diagnosed with quadriplegia (mean 49.4) self-reported more impaired HRQOL than children with diplegia (mean 69.1) and hemiplegia (mean 72.4). Parent–child concordance was lowest for emotional functioning. Providers and parents should obtain the children's HRQOL perceptions whenever possible.

Development of literacy skills was studied in six children (one male, five females) with severe speech impairments and cerebral palsy (CP). These skills were related to intellectual development, phonological abilities, and short-term memory. Three of the children were diagnosed with dystonia, and three with diplegia. They had no, or severely restricted, independent mobility (Gross Motor Function Classification System Level IV for four children and Level V for two), and severe fine motor problems, including difficulty with pointing. As they had no intelligible speech, the Bliss system was the primary communication mode. Assessments were made at approximately 6, 9, and 12 years of age. The results revealed that the children had difficulties acquiring literacy skills, although intellectual level and phonological ability predicted otherwise. Positive development during the first 3 years was followed by an arrest. A conspicuous decrease in IQ points was also found. Thus, phonological ability does not seem to have the same predictive power for literacy development in children with severe speech impairments and CP as in typically developing children. Further studies are needed to clarify the role of phonological abilities, working memory, and strategies used in literacy acquisition in these children. Such studies might also clarify the importance of articulatory abilities in early literacy acquisition.

There are a number of compelling reasons why sleep disorders should feature prominently in the training of paediatricians, child psychiatrists, and others involved in the care of children: (1) conservatively, 20 to 30% of children from infancy to adolescence have sleep problems which are considered significant by them or their parents; without effective treatment, these problems may persist for long periods; (2) sleep disturbance can harm a child's learning and behaviour, and, sometimes, physical development; (3) parenting and other aspects of family function can be seriously affected. In addition, the nature of the sleep disturbance, including its physiological aspects, might provide an insight into the mechanisms by which psychological disturbance is caused as a result of sleep loss or disruption.

A neuropsychological investigation of the association between specific language impairment (SLI) and hyperactivity was conducted on four groups of 6-year-old children. The groups, each consisting of five boys and five girls, were: children with SLI alone, hyperactivity alone, both SLI and hyperactivity, and neither disorder (controls). Cognitive functioning was examined using selected non-verbal tests from the Cambridge Neuropsychological Test Automated Battery. SLI was not associated with significantly reduced performance on any of the neuropsychological measures. However, hyperactivity was associated with deficits on a test of attentional set shifting previously demonstrated to be sensitive to frontostriatal dysfunction. Further, hyperactive children showed significantly reduced spatial spans on a test of spatial working memory thought to measure parietal lobe functioning. There were no substantial differences between the groups on tests of frontal lobe function except for reduced performance on a task of attention in the hyperactive group. There were no significant interactions between hyperactivity and SLI on any of the neuropsychological measures. The pattern of neuropsychological deficits shown by children with attention-deficit–hyperactivity disorder (ADHD) suggests relatively specific problems in inhibitory control of attentional selection. This cognitive deficit implicates brain areas including basal ganglia and ventro-lateral prefrontal cortical areas in ADHD, thus providing evidence for disruption of frontostriatal functional loops. SLI and hyperactivity can occur as comorbid syndromes or symptom complexes and this should be noted when interpreting results of tests measuring cognitive performance. The findings suggest that these two groups of disorders have different cognitive correlates.

The relationship of preterm birth to health-related quality of life (HRQoL) was examined for children aged 1 to 4 years. Three gestational age groups with a NICU history were selected, <32 weeks (n=65), 32 to 36 weeks (n=41), [ges ]37 weeks (n=54), and a reference group from the open population (n=50). The main instrument was the TNO-AZL Preschool Quality Of Life (TAPQOL) questionnaire, which was completed by the parents. In addition, other outcome measures obtained from parents or neonatologists were investigated. Children born <32 weeks had significantly lower HRQoL than the reference group in the scales for lungs, stomach, eating disorders, motor functioning, communication, and anxiety. Parental feelings towards the child were related to the child's HRQoL. We found differences between the neonatologists' and parents' perceptions of the children's situation, which can have clinical consequences (e.g. different opinions about what needed treatment). Neonatal intensive care after birth has HRQoL implications for all children, particularly in children born at <32 weeks of gestation.

Following the introduction of combination antiretroviral therapy, children vertically infected with the human immunodeficiency virus (HIV-1) living in the developed world are surviving into adult life. This paper reviews the neurodevelopmental outcomes of 62 consecutively-presenting children with HIV-1 infection diagnosed before 3 years of age (32 males, 30 females; median age at presentation 6mo). Neurological and developmental data are presented with immunological and virological responses to antiretroviral therapy. Fourteen children (22%) had abnormal neurological signs and 25 (40%) demonstrated significant developmental delay on standardized developmental assessments. Children presenting with more severe HIV-1 disease and immune compromise had significantly more abnormal neurological signs and developmental delays than children presenting with milder HIV-1 symptomatology. Immune function, control of HIV-1 viral replication, and growth parameters improved with antiretroviral therapy (median age at last follow-up 7y 3mo); however, abnormal neurological signs and significant gross motor difficulties persisted.

Nocturnal enuresis is a genetically determined maturational disorder of the central nervous system. Lack of arousal and an inhibition deficit of the micturition reflex have been found as the main dysfunctions leading to wetting during sleep. Both are mediated by nuclei in the brainstem. Therefore, evoked potentials (brainstem auditory evoked potential [BAEP], visual evoked potential [VEP], event-related late acoustic-evoked potential [P300]), and the prepulse inhibition (PPI) of the startle reflex were assessed to further evaluate the brainstem deficit compared with cortical function. Thirty-seven children with nocturnal enuresis, aged 8 years to 14 years 8 months (mean age 10y 7mo [SD 1y 10mo]; 27 males, 10 females) were compared with 40 controls (mean age 10y 7mo [SD 1y 6mo]; 17 males, 23 females). Left interpeak latencies I–III and I–V of the BAEP were increased in children with nocturnal enuresis. VEP measures did not differ between patients and controls. However, children with a positive family history of enuresis showed a shorter latency towards N75 and P100 than children without such a family history. P300 and PPI measures did not differ. We conclude that this strongly supports the postulation of a maturational deficit of the brainstem in nocturnal enuretic children. The increased interpeak latencies I–III and I–V of the BAEP support the hypothesis of an arousal deficit mediated by delayed maturation of brainstem function. Differences in VEP latencies might point towards functional cortical differences in children with a family history of nocturnal enuresis.

This study compared the passive stiffness of wrist flexors and the strength of wrist flexors and extensors in three different wrist positions (30° of flexion, neutral, and 30° of extension) between children with cerebral palsy (CP) and typically developing (TD) comparison children. It also examined associations between these characteristics and manual function in children with CP. Eleven children with spastic hemiplegic CP (six females, five males; mean age 8y 5mo [SD 1y 8mo], range 6–11y) and 11 TD children, matched for age and sex, took part in this study. Passive stiffness of muscles was measured as the torque/angle relation during passive motion. Isometric strength tests were performed and the time needed to complete three tasks based on the Jebsen–Taylor Hand Function Test was recorded. Flexor stiffness was higher in the group with CP. Strength of flexors and extensors in the group with CP was lower with the wrist extended. No difference among test positions was found in the TD group. Moderate correlations were observed between manual function and variables related to strength and stiffness of wrist muscles in the group with CP. Children with CP showed muscle alterations coherent with the use of the wrist in flexion. Intervention on these characteristics could have a positive impact on manual function.